Glucocerebrosidase (GBA) mutations occur frequently in Parkinson's disease (PD) patients. This study aims to identify potential crucial genes and pathways associated with GBA mutations in patients with PD and to further analyze new molecular mechanisms related to the occurrence of gene mutations from the perspective of bioinformatics. Gene expression profiles of datasets GSE53424 and GSE99142 were acquired from the Gene Expression Ominibus database. Differentially expressed genes (DEGs) were detected, using the 'limma' package in R, comparing IDI-PD 1 (idiopathic PD patients) and GBA-PD 1 [PD patients with heterozygous GBA mutations (GBA N370S)] group samples. The functions of top modules were assessed using the DAVID, whereas gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Protein-protein interaction networks were assembled with Cytoscape software and separated into subnetworks using the Molecular Complex Detection Algorithm. Data from GSE53424 and GSE99142 were also extracted to verify our findings. There were 283 DEGs identified in PD patients heterozygous for GBA mutations. Module analysis revealed that GBA mutations in PD patients were associated with significant pathways, including Calcium signaling pathway, Rap1 signaling pathway and Cytokine-cytokine receptor interaction. Hub genes of the two modules were corticotropin-releasing hormone (CRH) and Melatonin receptor 1B (MTNR1B). The expression of CRH was downregulated, whereas that of MTNR1B was upregulated in PD patients with GBA mutations. The expression of CRH and MTNR1B has diagnostic value for PD patients with heterozygous GBA mutations. Novel DEGs and pathways identified herein might provide new insights into the underlying molecular mechanisms of heterozygous GBA mutations in PD patients.

中文翻译：

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葡萄糖脑苷脂酶基因突变患者帕金森病相关基因和分子通路的生物信息学分析和鉴定。

葡萄糖脑苷脂酶 (GBA) 突变频繁发生在帕金森病 (PD) 患者中。本研究旨在寻找PD患者GBA突变相关的潜在关键基因和通路，并从生物信息学角度进一步分析与基因突变发生相关的新分子机制。数据集 GSE53424 和 GSE99142 的基因表达谱是从 Gene Expression Ominibus 数据库获取的。使用 R 中的“limma”包检测差异表达基因 (DEG)，比较 IDI-PD 1（特发性 PD 患者）和 GBA-PD 1 [具有杂合性 GBA 突变 (GBA N370S) 的 PD 患者] 组样本。使用DAVID评估顶部模块的功能，同时进行基因本体论和京都基因和基因组百科全书途径富集分析。使用 Cytoscape 软件组装蛋白质-蛋白质相互作用网络，并使用分子复合物检测算法将其分成子网络。还提取了 GSE53424 和 GSE99142 的数据来验证我们的发现。在 PD 患者中鉴定出 283 个具有 GBA 突变杂合子的 DEG。模块分析显示PD患者的GBA突变与重要通路相关，包括钙信号通路、Rap1信号通路和细胞因子-细胞因子受体相互作用。这两个模块的中心基因是促肾上腺皮质激素释放激素（CRH）和褪黑素受体1B（MTNR1B）。GBA突变的PD患者中CRH表达下调，而MTNR1B表达上调。CRH和MTNR1B的表达对于GBA杂合突变的PD患者具有诊断价值。本文确定的新的 DEG 和途径可能为 PD 患者杂合 GBA 突变的潜在分子机制提供新的见解。